Atopic dermatitis is a chronic inflammatory skin disease characterized in a persistent Pruritus and acute and chronic eczematous lesion of skin and may be accompanied by asthma, Allergic rhinitis and the like, in addition to the lesion of skin. As a cause of atopic dermatitis, skin barrier abnormality, etc., greatly except for a genetic factor, immunological factor and environmental factor, is recently considered as a major cause. In addition, it has been reported that atopic dermatitis is occurred by a lack of γ-linolenic acid in lipid and by a secretion of cytokine or chemokine.
Chemokine plays an important role in inflammatory cell infiltration in skin, and eotaxin-1, being C-C chemokine, is particularly increased in such a lesion of dermatitis, which is closely related to chemotaxis of eosinophil having C-C chemokine receptor 3 (CCR3) and Helper-T cell Type 2 (Th2).
Eotaxin-1 is expressed on various kinds of cells such as eosinophil, lymphocyte, macrophage, fibroblast, smooth muscle cell, epithelial cell, and the like, and plays an important role in attracting eosinophil into a lesion of dermatitis. Since eosinophil secretes a proteinous radical which has a very strong toxicity and a free radical, it can kill microorganisms and parasites, but if it is improperly activated, it can cause serious tissue damage and thus should be regulated very strictly. When such eosinophil moves from circulating blood to the tissue, the key material is eotaxin-1, and eotaxin-1 secreted from tissues of inflammatory region binds to CCR3 receptor on a surface of eosinophil to achieve the movement of eosinophil to inflammatory lesion. Therefore, the skin inflammatory reaction can be prevented by effectively regulating an expression of eotaxin-1 and CCR3.
Atopy is one of the important diseases mainly emerged in the advanced country since the 1970's, and is a growing trend all around of world and has a report that a prevalence rate thereof is 20% of the population of the world. There are 1.5 million of people having atopy in U.S.A. and 16.3% of elementary/middle/high school students have atopy in Korea. (Ahn S. Y. et al., J. Skin Barrier Res., 8, 47-51, 2006). At present, a steroid agent, topical immunosuppressive drug, anti-histamine agent, and the like are used as a medicine of atopic dermatitis, but when the above drugs are used for a long time, since there are problems such as thinning of the skin, discoloration of the skin color, osteoporosis, sclerosis of the arteries, possibility of carcinogenesis, worsening symptoms due to a resistance and the like, the development of the composition having an excellent anti-inflammation effect, while being safety because of the deriving thereof from a natural substance, is being made.
Meanwhile, Citrus unshiu is an evergreen tree of Citrus genus, Rutaceae family, and reseeds in Jeju-island in Korea, and is known to widely distribute in Japan, China, Latin America, the Black see, and the like. A fruit of Citrus tree is edible itself as well as 20% or more of it is consumed as a processing product such as juice, canned foods, and the like, and has plentiful fruit juice, unique flavor and high functional ingredients. For example, citrus contains materials such as d-limonene, linalool, linalylacetate as sesame flavor, hesperidin, naringin, poncirin, nobiletin as flavonoid, Synephrine, pectin, ascorbic acid, beta-cryptoxanthin, courin as alkaloid, and the like, and they are known to have stimulation of digestive organs, obesity, cough, blood-pressure-rising, anti-allergic, antimicrobial function, and the like.
But, a price of Citrus has been decreased sharply because of the unripe Citrus fruit and shipping of Citrus lowered in the quality due to the environmental changes such as the recent frequent rains, moisture, temperature, and the like, the mass-production via a protected cultivation such as a greenhouse and preference for imported citrus. Therefore, in order to reduce amounts of production of Citrus and gentrify the quality of Citrus, countermeasures such as in-advance harvest for unripe Citrus and the treatment, a thorough selection and quality control for Citrus, and development of a functional composition by using unripe Citrus has been prepared. As one example, many studies for isolating biological active substances from the unripe Citrus in-advance harvested or development of use by using them, are being made.
As the techniques related to the above, Korean Registered Patent No. 1259791 discloses a method for manufacturing a health supplement food by using Citrus flavonoid contained in an unripe Citrus and the health supplement food using it, Korean Registered Patent No. 1162761 discloses a composition for preventing or treating obesity comprising an unripe Citrus extract, and Korean Registered Patent No. 01315212 discloses an antidepressant containing the extract isolated from an unripe citrus pericarp of Citrus unshiu tree.
Therefore, inventors of the present invention studied the utilization plan for unripe Citrus fruit, found that the unripe Citrus fruit extract and synephrine have an excellent effect in treating an inflammatory skin disease and then have completed the present invention.